• Je něco špatně v tomto záznamu ?

A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma

S. Knop, M. Szarejko, N. Grząśko, S. Bringhen, K. Trautmann-Grill, A. Jurczyszyn, A. Vacca, C. Khandanpour, B. Gamberi, L. Pour, KF. Iversen, MT. Stumpp, C. Suter, KM. Dawson, C. Zitt, P. Legenne, V. Stavropoulou, MF. Fey, N. Leupin, H. Goldschmidt

. 2024 ; 5 (5) : 940-950. [pub] 20240801

Status neindexováno Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25002437

MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis. In this open-label, single-arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor- and/or immunomodulatory drug-relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen. Thirty-three patients received at least one dose of MP0250. The most frequent treatment-related adverse events were arterial hypertension (58.1%), thrombocytopenia (32.3%), proteinuria (29.0%) and peripheral oedema (19.4%). Of the 28 patients evaluable for response (median age: 60 [range 44-75]), nine achieved at least partial response, corresponding to an overall response rate of 32.1% (95% confidence interval [CI]: 17.9%, 50.7%), with a median duration of response of 8 months (95% CI 5-NR). An additional three patients achieved minimal response and nine stable diseases as the best overall response. Overall median progression-free survival was 4.2 months (95% CI 1.9-7.1). These findings are in line with the results of recent trials testing new agents on comparable patient cohorts and provide initial evidence of clinical benefit for patients with refractory/relapsed MM treated with MP0250 in combination with bortezomib/dexamethasone. Further clinical evaluation in the emerging MM treatment landscape would be required to confirm the clinical potential of MP0250.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc25002437
003      
CZ-PrNML
005      
20250123101933.0
007      
ta
008      
250117s2024 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1002/jha2.968 $2 doi
035    __
$a (PubMed)39415900
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Knop, Stefan $u Universitätsklinikum Würzburg Würzburg Germany $1 https://orcid.org/0000000312766639
245    12
$a A phase 1b/2 study evaluating efficacy and safety of MP0250, a designed ankyrin repeat protein (DARPin) simultaneously targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), in combination with bortezomib and dexamethasone, in patients with relapsed or refractory multiple myeloma / $c S. Knop, M. Szarejko, N. Grząśko, S. Bringhen, K. Trautmann-Grill, A. Jurczyszyn, A. Vacca, C. Khandanpour, B. Gamberi, L. Pour, KF. Iversen, MT. Stumpp, C. Suter, KM. Dawson, C. Zitt, P. Legenne, V. Stavropoulou, MF. Fey, N. Leupin, H. Goldschmidt
520    9_
$a MP0250 is a designed ankyrin repeat protein that specifically inhibits both vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor (HGF), aiming at potentiating cancer therapy by disrupting the tumour microenvironment. Encouraging results from a phase 1 trial of MP0250 in patients with solid tumours prompted further investigation in multiple myeloma (MM) as both MP0250 targets are reported to be drivers of MM pathogenesis. In this open-label, single-arm phase 1b/2 study (NCT03136653) in patients with proteasome inhibitor- and/or immunomodulatory drug-relapsed or refractory MM, MP0250 was administered every 3 weeks with standard bortezomib/dexamethasone regimen. Thirty-three patients received at least one dose of MP0250. The most frequent treatment-related adverse events were arterial hypertension (58.1%), thrombocytopenia (32.3%), proteinuria (29.0%) and peripheral oedema (19.4%). Of the 28 patients evaluable for response (median age: 60 [range 44-75]), nine achieved at least partial response, corresponding to an overall response rate of 32.1% (95% confidence interval [CI]: 17.9%, 50.7%), with a median duration of response of 8 months (95% CI 5-NR). An additional three patients achieved minimal response and nine stable diseases as the best overall response. Overall median progression-free survival was 4.2 months (95% CI 1.9-7.1). These findings are in line with the results of recent trials testing new agents on comparable patient cohorts and provide initial evidence of clinical benefit for patients with refractory/relapsed MM treated with MP0250 in combination with bortezomib/dexamethasone. Further clinical evaluation in the emerging MM treatment landscape would be required to confirm the clinical potential of MP0250.
590    __
$a NEINDEXOVÁNO
655    _2
$a časopisecké články $7 D016428
700    1_
$a Szarejko, Monika $u Uniwersyteckie Centrum Kliniczne Gdansk Poland
700    1_
$a Grząśko, Norbert $u Department of Experimental Hematooncology Medical University of Lublin and Centrum Onkologii Ziemi Lubelskiej Lublin Poland $1 https://orcid.org/0000000177274307
700    1_
$a Bringhen, Sara $u SSD Clinical Trial in Oncoematologia e Myeloma, Dipartimento di Oncologia Azienda Ospedaliera-Universitaria Città della Salute e della Scienza di Torino Torino Italy
700    1_
$a Trautmann-Grill, Karolin $u Universitätsklinikum Dresden, Technische Universität Dresden Dresden Germany $1 https://orcid.org/0000000290501049
700    1_
$a Jurczyszyn, Artur $u Plasma Cell Dyscrasias Center, Department of Hematology Jagiellonian University Medical College Krakow Poland
700    1_
$a Vacca, Angelo $u Department of Precision and Regenerative Medicine and Ionian Area Unit of Medicina Interna "Guido Baccelli" University of Bari Aldo Moro Azienda Policlinico Bari Italy $1 https://orcid.org/0000000245678216
700    1_
$a Khandanpour, Cyrus $u Universitätsklinikum Münster, Münster, Germany and University Hospital Schleswig-Holstein Campus Lübeck University Cancer Center Schleswig-Holstein, and University of Lübeck Lübeck Germany $1 https://orcid.org/0000000346556269
700    1_
$a Gamberi, Barbara $u AUSL-IRCCS Reggio Emilia Reggio Emilia Italy $1 https://orcid.org/0000000336165838
700    1_
$a Pour, Ludek $u Fakultní Nemocnice Brno Brno Czechia
700    1_
$a Iversen, Katrine F $u Lillebaelt Hospital Vejle Denmark $1 https://orcid.org/0000000344949034
700    1_
$a Stumpp, Michael T $u Molecular Partners AG Zurich-Schlieren Switzerland $1 https://orcid.org/0000000173562061
700    1_
$a Suter, Cosima $u Molecular Partners AG Zurich-Schlieren Switzerland
700    1_
$a Dawson, Keith M $u Molecular Partners AG Zurich-Schlieren Switzerland $1 https://orcid.org/000000021770291X
700    1_
$a Zitt, Christof $u Molecular Partners AG Zurich-Schlieren Switzerland
700    1_
$a Legenne, Philippe $u Molecular Partners AG Zurich-Schlieren Switzerland
700    1_
$a Stavropoulou, Vaia $u Molecular Partners AG Zurich-Schlieren Switzerland $1 https://orcid.org/0000000230002205
700    1_
$a Fey, Martin F $u Molecular Partners AG Zurich-Schlieren Switzerland
700    1_
$a Leupin, Nicolas $u Molecular Partners AG Zurich-Schlieren Switzerland
700    1_
$a Goldschmidt, Hartmut $u Medical Department V Universitätsklinikum Heidelberg Heidelberg Germany $1 https://orcid.org/0000000309610035
773    0_
$w MED00209731 $t EJHaem $x 2688-6146 $g Roč. 5, č. 5 (2024), s. 940-950
856    41
$u https://pubmed.ncbi.nlm.nih.gov/39415900 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20250117 $b ABA008
991    __
$a 20250123101927 $b ABA008
999    __
$a ok $b bmc $g 2254576 $s 1238440
BAS    __
$a 3
BAS    __
$a PreBMC-PubMed-not-MEDLINE
BMC    __
$a 2024 $b 5 $c 5 $d 940-950 $e 20240801 $i 2688-6146 $m EJHaem $n EJHaem $x MED00209731
LZP    __
$a Pubmed-20250117

Najít záznam

Citační ukazatele

Možnosti archivace